Cardiac Paraganglioma
Cardiac paragangliomas are unusual extra-adrenal tumors, originating in chromaffin cells of the sympathetic ganglia. Cardiac paragangliomas, which have variable features and symptoms based upon tumor location, size, and hormonal activity, are often difficult to diagnose and manage. Protheragen is a full-service company for drug discovery and development committed to serving the special needs of rare cardiovascular diseases, including cardiac paraganglioma.
Introduction to Cardiac Paraganglioma
Cardiac paraganglioma is an uncommon tumor that commonly manifests as a large, highly vascular tumor that encases vital cardiac structures. It may develop from any of the chambers.
Symptoms may occur due to catecholamine secretion in functionally active cardiac paragangliomas and also mass effect, as these tumors are usually large by the time they are diagnosed. These tumors are usually soft and fleshy, lacking any distinct capsule. They are highly vascular and most frequently parasitize the blood supply from the coronary arteries.
Fig.1 The assessment and therapy of cardiac paraganglioma. (Chan, E. Y., et al., 2022)Pathogenesis of Cardiac Paraganglioma
The pathogenesis of the cardiac form is closely related to genetic mutations, and a high percentage are associated with germline or somatic mutations of the genes of the succinate dehydrogenase (SDH) enzyme complex, especially SDHB, SDHC, and SDHD. Mutations in these genes cause the accumulation of succinate, blocking prolyl hydroxylase enzymes and stabilizing hypoxia-inducible factor (HIF)-1α. Such stabilization leads to a pseudohypoxia state of the cells, activating the downstream genes associated with cellular proliferation, angiogenesis, and dysregulated metabolism, thereby promoting cancer formation. Other rare associated genetic mutations are VHL, RET, and NF1.
Fig.2 Genetic mutation profiles of cardiac paragangliomas in SDH enzyme subunit genes. (Tella, S. H., et al., 2020)Therapeutics Development for Cardiac Paraganglioma
| Drug Name | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|
| Doxazosin | It attaches reversibly to postsynaptic alpha-1 receptors on the vascular smooth muscle, leading to vasodilation and diminished peripheral vascular resistance systemically. | Alpha-1 adrenergic receptors | Approved |
| Sunitinib | Antiangiogenic and antitumor cell proliferation effects due to a multi-targeted receptor tyrosine kinase inhibitor. | VEGFR, PDGFR, KIT, RET, CSF1R | Approved |
| Cabozantinib | Multi-targeted receptor tyrosine kinase inhibitor acting on angiogenesis and also on metastasis and tumor proliferation pathways. | MET, VEGFR2, RET | Approved |
| Belzutifan | Inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α), which interrupts a critical pathway in some paraganglioma malignancies. | HIF-2α | Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
One-stop integrated services of our company, from diagnostics and therapeutics to the establishment of strong disease models and reliable preclinical studies, every step is covered! We have the knowledge and experience not only in basic research but also in critical pharmacokinetics and drug safety. The pharmacokinetics and toxicity of a drug are crucial for drug development. We give our partners the tools and knowledge they need to quickly advance their drug development pipelines for rare heart disease.
Therapeutic Development Services
Diverse Platforms
Animal Model Development for Cardiac Paraganglioma
The development of an adequate animal model for cardiac paraganglioma is essential for providing knowledge of the origin of this tumor and guiding the therapeutic approach. They serve as an essential stage where candidate drugs can be reviewed and tested for safety and efficacy prior to human trials. Understanding the special challenges cardiac paraganglioma pose, we specialize in offering custom animal model development, as well as the ability to provide such high-quality, target-relevant, preclinical tools needed to fuel your drug discovery and development programs.
Genetically Engineered Animal Models
These models involve manipulating specific genes known to be associated with paraganglioma development, often in mice, to mimic the human disease.
Optional models: Sdhb-/- model, other models.
Pharmacokinetics and Drug Safety Research Services
Protheragen's dedication to scientific excellence, coupled with our profound knowledge of diseases such as cardiac paraganglioma, places us at the forefront of the rare disease industry. Our proprietary advanced methodologies and client-centric approach result in high-quality, actionable results. Reach out and find out how our integrated services can speed your path from discovery to market.
References
- Chan, Edward Y et al. "Management of primary cardiac paraganglioma." The Journal of thoracic and cardiovascular surgery 164.1 (2022): 158-166.
- Tella, Sri Harsha et al. "Comprehensive review of evaluation and management of cardiac paragangliomas." Heart (British Cardiac Society) 106.16 (2020): 1202-1210.
For research use only, not for clinical use.